The present invention relates to a process for the preparation of gemfibrozil.
Gemfibrozil, or 2,2-dimethyl-5-(2,5-xylyloxy)-valeric acid, of formula (I): ##STR2## is a known hypolipemizing medicament widely used.
In USA, the market value of gemfibrozil in 1992 was estimated to be about 550 million dollars (SCRIP n. 1792, 5-2-93, p 7).
Therefore, it is evident the importance of methods allowing to prepare gemfibrozil in a cost-saving and industrially convenient way.
The up to now known methods do not solve satisfactorily the problem.
U.S. Pat. No. 3,674,836 discloses the reaction of a 3-(2,5-xylyloxy)propyl halide with an isobutyric acid 2-lithium derivative, to give compound (I). However, the use of lithium derivatives and anhydrous solvents involves evident drawbacks.
EP-219117 and JP-63 190 883 (Nitto Chemicals) disclose the preparation of .varies.,.varies.-dimethyl-5-valerolactone by radicalic addition of HBr to 2,2-dimethyl-4-pentenoic acid and subsequent cyclization to lactone in alkali medium. The resulting compound was used by the Applicant as an intermediate for the preparation of gemfibrozil.
Finally, U.S. Pat. No. 4,665,226 envisages the reaction of 2,5-dimethylphenol with an 5-bromo- or 5-chloro-2,2-dimetilpentanoic acid ester, in a mixed solvent system (generally toluene/dimethylsulfoxide) under reflux for a time ranging from 7 to 20 hours.
The use of high-boiling solvents, which are difficult to remove, the high temperatures and the long reaction times make such a process scarcely attracting from the industrial point of view.